Co-translational assembly of multiprotein complexes: a systems biology approach

点击翻译按钮获取中文摘要

The information to build a cell is carried in its DNA. To be used, a portion of DNA needs to be copied into another molecule called RNA, from which it can be 'translated' into a protein. Proteins are the components that directly build the cell and make it function. Proteins do not work on their own. They attach to each other to form complicated machines, sometimes made up of dozens of proteins. Groups of proteins that are bound to each other and work together are called protein complexes. Not much is known about how protein complexes are built by cells. One possibility is that proteins are first made, and then attach to each other to form a complex. A second possibility is that the proteins start to bind to each other while they are being made in the cell. There are a few known cases of protein complexes that are made in the second way. However, because detecting this phenomenon is very difficult, it is not known if cells usually choose this way of making protein complexes. I have recently developed methods that make it easy to tell if the formation of a complex proceeds in this way. The aim of this project is to apply this method to many protein complexes with very different functions, in order to understand how cells build protein complexes. Why is this important for a cell? There are several reasons. Proteins need to recognise each other to form protein complexes, and they can recognise each other because they have specific shapes that fit into each other (similar to a key fitting into a lock). The shape of a protein changes as it is being made, and it is possible that some proteins can no longer fit into each other once they are completely made. Also, some proteins may be toxic for the cell when they are free (but useful when they are part of the correct complex). A good way to avoid this is to put the proteins in the complex as soon as possible (even before they are finished). We will study these questions using simple yeast cells. Yeast cells are similar enough to us that what we can learn from them is useful to understand the human body. Because protein complexes are important for almost everything a cell does, we hope that understanding how they are made by cells will help understand how they function and what goes wrong with them during disease.